The invention herein is directed to a new pharmaceutical composition which consists of a generally trilayer tablet having an inner core, an intermediate barrier coating and an outer mantle coating surrounding the inner core. The inner core includes the NSAID ibuprofen or a salt of ibuprofen. The mantle coating includes a prostaglandin, described hereinafter in more detail.
Nonsteroidal anti-inflammatory drugs (NSAIDs) comprise a class of drugs which have long been recognized as having high therapeutic value especially for the treatment of inflammatory conditions such as exhibited in inflammatory diseases like osteoarthritis (OA) and rheumatoid arthritis (RA). While the NSAIDs present a beneficial therapeutic value they also exhibit undesirable side effects. An especially undesirable side effect of the administration of NSAIDs is the ulcerogenic effects generally associated with chronic use. The chronic use of NSAIDs, the use of high dosages of NSAIDs and the use of NSAIDs by the elderly can lead to NSAID induced ulcers. NSAID induced ulcers in the stomach can be dangerous. Such ulcers generally exhibit little or few symptoms and may cause dangerous bleeding when undetected. In some instances, bleeding ulcers can prove fatal. The U.S. Food and Drug Administration requires a class warning for all NSAIDs, which states: Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation can occur at any time, with or without warning symptoms, in patients treated chronically with NSAID therapy.
Certain prostaglandins have been shown to prevent NSAID induced ulcers. Acceptable prostaglandin compounds for the invention herein and their preparation are described in U.S. Pat. Nos. 3,965,143, 4,060,691, 4,271,314, and 4,683,328. The prostaglandin compound commercially available under the USAN (United States Adopted Name) name misoprostol is a pharmaceutically acceptable prostaglandin which has been accepted for use in the treatment of NSAID induced ulcers in many countries, including the United States. Misoprostol is commercially available as a stabilized formulation by prescription in such countries. The stabilized formulation is described in U.S. Pat. No. 4,301,146.
While prostaglandins are beneficial compounds and have found therapeutic usage, prostaglandins are generally considered highly unstable. Therefore, it is desirable to find prostaglandins with the desired anti-ulcerogenic properties and which can be stabilized or provided in stabilized formulations especially with respect to contemplated oral methods of delivery.
It would be desirable to provide a pharmaceutical composition which would exhibit the beneficial properties of an NSAID and which composition would exhibit the beneficial properties of a prostaglandin for countering (by inhibiting, reducing or preventing) the ulcerogenic side effects attendant to NSAID administration.